Decreased Meal Size Research Articles

Ginsenoside-Rb1 as a suppressor in central modulation of feeding in the rat

Ginsenosides, the main component of Panax ginseng root, have been reported to show several pharmacological actions on the peripheral metabolism of glucose and lipid and on endocrine secretion. The present study aimed to clarify the effects of ginsenoside-Rb1 on feeding behavior and endogenous chemical substances. Rb1 infusion into the rat third cerebroventricle was started at 1930 hr, and ingestive behavior was recorded in a soundproof room illuminated daily from 0800 to 2000 hr. Rb1 at doses of 0.05, 0.10 and 0.20 mumol potently decreased food intake dose-dependently during the first dark period after infusion. Analysis of meal patterns revealed that the suppressive effect was due to decreasing meal size, but not to postprandial intermeal interval and eating speed. Drinking episodes decreased concomitantly with feeding suppression only at the highest dose of 0.20 mumol. Ambulatory activity was not affected in the doses tested. Infusion of Rb1 increased plasma glucose, leaving insulin unaffected. Microinjection of 0.01 mumol Rb1 into the hypothalamic ventromedial nucleus (VMH) decreased food intake, but injection into the lateral hypothalamic area did not. Taking these data together, Rb1 was found to have a suppressive effect on feeding partly through the VMH.

Glucagon-(1–21) fails to inhibit meal size in rats

Rats were intraperitoneally injected with 115 or 230 nmol/kg pancreatic glucagon or equimolar doses of glucagon-(1–21) just before refeeding at the beginning of the dark phase after a 12 hr period of food deprivation. Glucagon-(1–21) and pancreatic glucagon have been reported to have similar visceral effects, but glucagon-(1–21) does not have pancreatic glucagon's metabolic effects. In this experiment, both doses of pancreatic glucagon, but neither dose of glucagon-(1–21), significantly decreased meal size. This indicates that the C-terminal octapeptide of pancreatic glucagon is necessary for its satiety effect, just as it is for its metabolic effects.

Infusion of CCK-8 into hepatic-portal vein fails to reduce food intake in rats.

If the putative satiating effect of endogenous cholecystokinin (CCK) is produced through a circulating hormonal mechanism, then administration of exogenous CCK into the hepatic-portal vein should decrease meal size. To test this, one form of endogenous CCK, the C-terminal octapeptide CCK-8, was infused intraportally in doses of 4 and 8 micrograms/kg just prior to a test meal. Neither dose decreased food intake after intraportal infusion even though intraperitoneal administration of 4 micrograms/kg CCK-8 decreased meal size approximately 50% in the same rats. The results suggest that if endogenous CCK-8 has a satiating effect, it acts primarily through a paracrine mechanism.

Infusion of cholecystokinin between meals into free-feeding rats fails to prolong the intermeal interval

The sulfated octapeptide of cholecystokinin (CCK-8) was infused intraperitoneally into 7 free-feeding male Sprague Dawley rats over a 6-day period. Infusions were given near the end of each free-feeding meal (1.87 μg/meal/rat), and also during the intermeal interval in gradually increasing doses (0.10-0.63 μg/5 min/rat). Food intake was continuously monitored and the infusions were controlled by microcomputer. Meal patterns, total food intake, and body weights during drug infusion were compared with data collected during a baseline period when only saline was infused. Meal-contingent CCK-8 infusion produced a significant 29.9% decrease in meal size which persisted throughout the drug-infusion period. Intermeal infusion of CCK-8 failed to prolong the intermeal interval (IMI) but it did initially prevent the compensatory decrease in IMI and increased feeding frequency expected after meal size was reduced. By the last day of drug infusion, total daily food intake recovered to baseline levels due to increased feeding frequency. Body weight was only transiently reduced by CCK-8 infusion. These findings show that (1) tolerance does not develop to the action of CCK-8 to suppress meal size, and (2) the administration of exogenous CCK-8 to free-feeding rats does not persistently prolong the intermeal interval.

Hypothalamic serotonin in the control of meal patterns and macronutrient selection

Serotonin (5-HT) is believed to have an inhibitory influence over feeding behavior. The present experiments were designed to investigate the effects of hypothalamic 5-HT on spontaneously motivated feeding and appetite regulation. Freely-feeding rats were injected with 5-HT or norfenfluramine (NORFENF) directly into the paraventricular hypothalamus (PVN), and precise changes in feeding behavior were monitored by a computer. Following PVN 5-HT or NORFENF injection, animals exhibited a marked suppression in food intake, associated with a decrease in meal size, duration and eating rate and no change in the frequency of meals consumed. This suggests that brain 5-HT may influence primarily the induction of satiety rather than the suppression of hunger. The effect of drugs presumed to affect brain 5-HT transmission on diet selection was also investigated in groups of rats injected centrally with 5-HT or NORFENF or peripherally with either fenfluramine, quipazine or cyproheptadine. In a series of 2-diet tests, rats centrally injected with 5-HT or NORFENF exhibited a selective suppression of the carbohydrate-rich diets. In animals provided with three pure macronutrient diets, protein, carbohydrate and fat, systemic administration of serotonergic agents had its greatest impact on fat and carbohydrate ingestion, as compared to protein consumption. These findings support a role for hypothalamic 5-HT in modulating meal patterns and appetite for particular macronutrients.

Intraventricular bombesin can decrease single meal size in the baboon

We have reported that intravenous bombesin decreases single meal size in a dose-dependent manner [12]. The present study tests whether intraventricular bombesin is also effective in decreasing single meal size. Doses of bombesin (0.1–4 μg/kg) were administered both intravenously and intraventricularly. A median dose of 1 gmg/kg bombesin decreased 30 min meal size about 50%, whereas a median dose of 1 μg/kg given intravenously only decreased meal size 25%. We conclude that bombesin given centrally in the baboon can decrease meal size and that this effect does not appear to be due to leakage into the periphery.

Effect of CCK-8 on basal and meal-stimulated somatostatin in the baboon

We measured the ability of CCK-8 alone, a test meal alone, or a combination of the two, to increase peripheral plasma somatostatin levels in the baboon. Baboons received a five-minute intravenous infusion of either CCK-8 (1, 2, or 4 μg/kg) or saline prior to a 30-minute meal. CCK-8 administration at all doses resulted in a significant rise of plasma somatostatin-like immunoreactivity (SLI). In addition, ingestion of a meal following a control saline infusion resulted in a significant rise of plasma SLI. However, the meal-related rise in SLI was blunted by prior administration of CCK-8 at all doses, including a dose which did not significantly decrease meal size. CCK-8 administration at all doses also blunted the meal-related rise of plasma insulin and glucose. We conclude that the known ability of CCK-8 to inhibit gastric emptying, as well as to decrease meal size, may account for its suppression of the meal-related SLI release.

Anorexia induced in rat by D-glucosamine deoxidized at C-1.

The effects of D-glucosamine (2-amino-2-deoxy-D-glucose), an endogenous glucose analogue, and 1-deoxy-D-glucosamine on feeding behavior were clarified. Test solutions (24 mumol) were infused into the third cerebroventricle of the rat. Glucosamine induced a feeding episode within 30 min after infusion and then prolonged the ensuing postprandial intermeal interval for the first 4 h of the dark period, while glucose suppressed feeding by decreasing meal size. Ventricular injection of 1-deoxyglucosamine potently suppressed feeding in a dose-related manner by affecting all meal parameters, and oral administration of 2,400 mumol also induced anorexia. Changes in activity of glucose-sensitive neurons in the lateral hypothalamus and glucoreceptor neurons in the ventromedial hypothalamus after electrophoretic application of glucosamine and 1-deoxyglucosamine were compatible with behavior changes. The results indicate that replacement of a hydroxyl group by an amino group at C-2 of the glucose molecule affects feeding behavior and deoxidation of C-1 potently induces anorexia.

1-Deoxy-glucosamine initiates, then effectively suppresses feeding in the rat

The deoxy analogues of D-glucose, 1-deoxy-D-glucosamine and D-glucosamine, are biochemically and structurally similar to 1-deoxy-D-glucose, so their direct effects on food intake were studied. Both 12 and 24 μmol 1-deoxy-glucosamine potently decreased feeding and body weight after an initial transient elicitation of food intake. The suppression included decreased meal size and prolonged postprandial intermeal interval which persisted for at least 3 days after injection. Ambulatory activity was unaffected. The initial elicitation of feeding was not accompanied by drinking episodes, and subsequent drinking suppression was persisted. These findings, plus other biochemical evidence, suggest that inversion with an amino group or removal of a hydroxyl group from C-2 and/or C-1 may effect feeding.

Feeding Pattern Responses to Changes in Dietary Energy or Environmental Temperature in the Domestic Fowl

Two experiments using 64-week-old Single Comb White Leghorn roosters were conducted to determine the meal response to an abrupt change in dietary energy or environmental temperature. In the first experiment, dietary energy level was changed from 200 kcal to either 250 or 150 kcal/75 g. In the second experiment, environmental temperature was changed from 22.2 C to either 13.3 or 30.0 C. Feeding behavior was recorded throughout both experiments. Meal size, meal frequency, and time spent eating a meal were measured.Roosters changed to high-energy or low-energy diets consumed low or high amounts of feed, respectively. Those fed the high-energy diet tended to decrease meal size and meal duration and to increase the number of meals. Roosters changed to the low-energy diet decreased meal size and meal duration and increased the number of meals eaten. The results tend to confirm the chemostatic mechanism in birds as food intake was related to energy in the diet.Roosters changed to high or low environmental temperature responded by decreasing or increasing their feed intake, respectively. Roosters changed to a high environmental temperature significantly decreased meal size, meal duration, and increased the number of meals. Those changed to a low environmental temperature significantly increased meal size and decreased meal frequency and meal duration.

Short-chain polyhydroxymonocarboxylic acids as physiological signals for food intake

In order to clarify the effects of endogenous organic acids on short and long-term feeding behavior, ingestive behavior was monitored for 2 hr before and after intra-third ventricular infusions of 3,4-dihydroxybutyric acid (2-deoxytetronic acid, 2-DTA), 2,4,5-trihydroxypentanoic acid (3-deoxypentonic acid, 3-DPA), and 3-hydroxybutyric acid (3-HBA). In addition, meal patterns were recorded for 2 days before and after the ventricular infusions. 2-DTA suppressed both short and long-term feeding by decreasing meal size (MS). 3-DPA elicited transient feeding behavior, but caused no change in long-term feeding. 3-HBA initially stimulated feeding, but subsequently suppressed long-term feeding by decreasing MS and prolonging postprandial intermeal interval (IMI). The suppressive effects of 3-HBA on feeding behavior lasted about 24 hr longer than those of 2-DTA. Based upon these observations as well as our previous reports, it appears that some of the processes affecting hunger and satiation are mediated by changes in central and peripheral concentrations of these organic acids.

Meal patterns and glucoprivic feeding in the guanethidine-sympathectomized, adrenodemedullated rat

The feeding behavior of rats sympathectomized by neonatal administration of guanethidine (GUA) and/or adult adrenal demedullation (MDL) was investigated. GUA treatment tended to decrease body weight gain and food intake, chiefly by decreasing meal size and increasing satiety ratios. It also attenuated the increase in food intake caused by 2-deoxy-D-glucose (2DG; 150, 300, 450 mg/kg, IP) but not by insulin (3, 6, 9 U/kg, IP). MDL altered meal patterns in the same manner as GUA treatment but the effects were of smaller magnitude. It did not influence the response to either glucoprivic challenge. Combined GUA treatment and MDL generally produced additive effects. These results suggest that the major sympathetic influence on feeding is through adrenergic innervation and not circulating catecholamines. The hypothesis that the alteration in feeding patterns produced by ventromedial hypothalamic lesions is due to decreased sympathetic activity was not supported.

Postgastric satiety in the sham-feeding rat

A sham-feeding model using rats fitted with gastric and duodenal cannulas was employed to investigate the role of postgastric mechanisms of satiety in the short-term control of food intake. When fasted rats sham fed a liquid diet [Vivonex High Nitrogen (VHN), 0.5 kcal/ml], food drained freely from gastric fistulas, and mean first-meal size and 90-min intake increased more than threefold. Varying the rate of duodenal infusion of diet during sham feeding (0.06-0.44 kcal/min) decreased first-meal size and total intake in a dose-dependent manner. First meals ended when mean loads of 2-3 kcal had been delivered. The threshold rate (0.11 kcal/min) decreased meal size and total intake by more than 50%. When fasted rats consumed VHN to satiety with closed gastric fistulas, rate of gastric emptying of diet during feeding averaged 0.32 +/- 0.02 kcal/min and the load emptied by meal termination averaged 3.8 +/- 0.2 kcal. These results indicate that rates of gastric emptying of diet and loads delivered to the small intestine following ingestion of liquid food are sufficient to elicit postgastric satiety in the absence of gastric distension.

The sites of action of cholecystokinin in decreasing meal size in pigs

The synthetic octapeptide of cholecystokinin (CCK-8) was infused at the rate of 67 ng/kg-minute into the jugular vein, carotid artery, portal vein, gastric branch of the splenic artery, and aortic artery both craniad and caudad to the origins of the cranial mesenteric and coeliac arteries of 39 young female pigs. Jugular, carotid and cranial erotic infusions resulted in significant reduction of meal size respectively to 65, 67 and 71% of control meal size (p less than 0.05). Gastric artery infusion resulted in a significant increase of meal size to 122% of control meal size (p less than 0.05). Portal vein and caudal aortic artery infusions had no significant effects on meal size. The results were interpreted as indicating a major site of action of CCK in reducing meal size in the bed of the cranial mesenteric or coeliac arteries, but excluding the stomach and liver.

Suppressive effects on food intake and its analysis following temporary and continuous intra-third ventricle administration of mazindol.

In order to clarify suppressive effects of mazindol (MZD) on food intake, its temporary or chronic infusion into the third ventricle was carried out. Changes in feeding patterns and endogenous chemical substances were determined following one shot infusion of 0.03 μmole MZD, as well as chronic infusion of 0.07 umole/day MZD using Alzet Minipump (Alza Corp.). MZD decreased meal size (MS) and increased postprandial intermeal interval (IMI), which led to enhanced satiety ratio (SR = IMI/MS) during only 4 hours following one shot infusion. On the other hand, chronic infusion of MZD continued to reduce food intake during 24 hours to the same extent as did one shot infusion. As for assaying of chemical substances in the plasma of fasted rats, MZD elicited a relative increase of glucose without hyperinsulinemia as well as a relative decrease of free fatty acids. These results were compatible with endogenous chemical changes in satiated states. Taken together with these findings, it was suggested that MZD reduced food intake, inhibiting the neuronal activities in the lateral hypothalamic area and/or accelerating those in the ventromedial hypothalamus.

Pancreatic glucagon and postprandial satiety in the rat

The hypothesis that administration of pancreatic glucagon inhibits feeding by eliciting satiety for food was tested against several behavioral and physiological criteria of specificity. The effects of intraperitoneal glucagon injections on intake of a palatable milk diet were tested in rats maintained with ad lib access to pelleted diet. Injections of 25–800 μg/kg glucagon administered at meal onset inhibited meal size by 17–36%, but did not affect the normal postprandial behavioral satiety sequence or elicit any behavioral signs of toxicity. Latency to rest and intermeal interval were not affected. Glucagon decreased meal size by specifically inhibiting feeding during the terminal phase of the meal without affecting feeding earlier in the meal. This was also the case when glucagon was injected 4 min prior to meal onset. This range of glucagon doses did not affect water intake in water deprived rats consuming fluid volumes comparable to the milk intakes. They also did not affect body temperature. Finally, injection of 400 μg/kg glucagon after the initial exposure to a novel drinking fluid was not sufficient to form a conditioned taste aversion in a two bottle preference test. These data, together with reports that circulating pancreatic glucagon levels increase during meals, strongly suggest that pancreatic glucagon is involved in the production of postprandial satiety.

Cholecystokinin inhibits food intake in genetically obese (C57BL/6J-ob) mice

Cholecystokinin (CCK, 20% pure) inhibited liquid food intake in obese and lean male mice after 1.5 and 4.5 hr of food deprivation. CCK decreased meal size without changing the duration of the postprandial intermeal interval. The inhibition of food intake was relatively specific. The largest dose of CCK tested (40 U/kg) had no effect on water intake in lean mice and it merely changed the pattern of intake in obese mice. Obese mice were as sensitive as lean mice to the satiating effect of CCK after 1.5 hr and 4.5 hr of food deprivation. Since CCK decreased meal size in obese mice and since obese mice were normally sensitive to CCK, CCK could be the circulating satiety factor that Coleman [4] postulated was deficient in obese mice. The results, however, only indicate that CCK could be the deficient factor. Other experiments are required to prove the point.

Feeding and drinking behavior responses of adult Zucker obese rats to cholecystokinin

Increased meal size in obese animals may occur because of decreased sensitivity to satiety factors. Feeding and drinking behavior responses of Zucker obese and lean rats to two forms of cholecystokinin (CCK), a putative satiety factor, were compared in these experiments. Octapeptide of CCK (CCK-8) in both obese and lean rats decreased meal size (47 and 65%) and rate of eating but not meal duration, and increased satiety ratio but not postmeal interval. Impure CCK decreased first meal size after a 6-hr fast similarly in obese and lean rats (33 and 40%, respectively); however, meal duration was decreased only in lean rats, and rate of eating was decreased only in obese rats. Postmeal interval was decreased in lean rats, while satiety ratio was increased only in obese rats. In spite of decreased first meal size daily food intakes were increased by both impure CCK and CCK-8 in lean rats. In 6-hr water-deprived rats injected with CCK-8, decreased water intake was associated with decreased food intake. However, while impure CCK in lean rats elicited similar responses as CCK-8, impure CCK in obese rats decreased food but not water intake. Feeding behavior response to the putative satiety agent, cholecystokinin, depended on form of the peptide administered and phenotype.

Monitoring the Effects of Selected Compounds on Feeding Behavior of Sheep1

A system for monitoring feed intake, meal number, meal size, meal time, meal interval and total time spent eating, is described. The system was used to study the effects of cyproheptadine, an appetite stimulant; a cyproheptadine methyl piperidine analog (CMPA); MK-940, a drug that blocks norepinephrine reuptake in the brain; and insulin after im injections on the feeding behavior of wether lambs. On control days, lambs consumed an average of 1,280 to 1,570 g of feed in 12 to 15 meals averaging 102 grams. Controls averaged 5.1 to 5.6 min per meal with intervals of 1.57 to 1.96 hr between meal starts and spent 65.2 to 85.6 min per day eating. Cyproheptadine stimulated feed intake during the 3 hr after dosing (P≤.05) by increasing meal frequency (P≤.10) and total time spent eating (P<.05). Feed consumption decreased after this period, so that cyproheptadine had no net effect on 24-hr feeding parameters. Insulin and CMPA had no effect on 24-hr feed intake although insulin increased the number (P≤.10) and decreased the size (P≤.05) of meals and CMPA decreased meal size (P≤.10). MK-940 reduced daily feed intake (P≤.05) and all feeding parameters appeared to be altered for 3 hr after dosing. MK-940 reduced meal size (P≤.05) and daily time spent eating (P≤.10).

Effects of jejunoileal bypass on meal patterns in genetically obese and lean rats.

Jejunoileal bypass surgery, designed to reproduce the human operation (long bypass) was contrasted with a short bypass of only a few centimeters of ileum in both genetically obese rats and their lean littermates. In comparison with the short-bypassed rats, long-bypassed rats of both genotypes lost weight and reduced food intake. When adjustments were made for group differences before surgery, no significant differences were detected in the effectiveness of the operation on the two genotypes. The reduction in food intake was accomplished by a decrease in meal size and an increase in intermeal interval. Food intake gradually returned in the long-bypassed rats toward its level in the short-bypassed rats. This increase was accomplished by an increase in meal size alone. Intermeal intervals remained prolonged. In the long-bypassed rats, compared with the short, meal duration was initially elevated and gradually increased more than did meal size, indicating a great slowing of eating rate. Water intake was unaffected, but water-to-food ratio was elevated initially and gradually declined in the long-bypassed rats. Learned food aversion, dehydration, and gastrointestinal and metabolic alterations due to malabsorption are mentioned as possible contributors to the reduction in food intake, but none of these alone can account for all the changes in meal pattern by which intake reduction is accomplished.